Terrence P O'Brien MD

Acute microbial keratitis may be caused by multiple bacterial species, ?lamentous fungi andyeasts, several important viruses, and less commonly parasites. Clinical evaluation shouldinclude assessment of the severity of the disease, construction of a differential diagnosis andidenti?cation of probable predisposing factors. Management of acute ulcerative, suppurativekeratitis is based on clinical severity. Non-invasive imaging with confocal microscopy andanterior optical coherence tomography can be bene?cial for diagnosis and clinical staging.Culture-directed versus empirical therapy is preferred. The choice of initial antibacterial agent(s)for therapy is based on the most commonly encountered bacterial pathogens, prevailing suscep-tibility data and resistance patterns, pharmacokinetic and pharmacodynamic parameters, bio-compatibility and safety features. Modi?cation of antimicrobial therapy is based upon clinicalresponse and laboratory susceptibility determination of recovered corneal pathogens. Use oftopical corticosteroids remains controversial and should only be initiated after adequate anti-bacterial therapy with suf?cient concentrations and duration to bring organism replication undercontrol. Other measures to counteract stromal keratolysis include systemic tetracyclines(doxycycline or minocycline), n-acetylcysteine 10%, ethylene diaminetetraacetic acid (EDTA) ormatrix metalloprotease inhibitors. The evolving role of collagen corneal cross-linking withapplication of topical ribo?avin and UV light is incompletely determined. Collagen cornealshields or therapeutic bandage soft contact lenses may provide protection and tectonic supportwith excessive thinning or impending perforation. Tissue bioadhesives may be applied foradditional tectonic support. Therapeutic keratoplasty should be considered for rapidly, progres-sive stromal keratolysis non-responsive to aggressive therapy. Compliance with frequent dosingschedules is imperative for treatment success. Newer methods of drug delivery may allowachievement of a therapeutic index with less frequent dosing, lowered cytotoxicity, bettertolerability and improved compliance.In summary, there have been signi?cant advances in the understanding of basic pathophysiologyof microbial keratitis over the last 25 years, yet there is still a somewhat primitive knowledge ofthe microbes and other possible pathogens. There has been relatively little attention to hostfactors and risks for developing infection. There have been marked improvements in resolutionof noninvasive ocular imaging modalities to aid diagnosis. Although there has been develop-ment of some newer antimicrobial agents, few address novel targets to circumvent resistance.Prevention of host tissue destruction is clearly lacking and a mandate for the future. Other futurestrategies include understanding microbial genomics, elucidating host gene expression duringinfectious keratitis and utilizing proteomics to target proteins in ocular infections both fordiagnosis and therapy.